Abstract: A method for determining the presence or amount of a target nucleic acid sequence in a sample, uses magnetic particles loaded with a probe and polystyrene particles loaded with a probe, in particular a different probe, for directly or indirectly detecting the presence or amount of the target nucleic acid sequence which is in particular indicative of a disease. The methods of the present invention allow for determining target nucleic acid sequences even in low abundance and in complex samples with advantageous sensitivity and, thus, represent promising approaches which can in particular be used in the diagnosis of several diseases and health conditions. A kit comprising a loaded magnetic particle and a loaded polystyrene particle is provided and can be used for the methods of the present invention, in particular for diagnosis or prognosis of a disease in a subject such as a human.